POTENTIATION OF THE HYPOTHALAMIC‐PITUITARY‐ADRENAL RESPONSE TO METYRAPONE BY l‐DOPA IN ACROMEGALIC PATIENTS

Abstract

SUMMARY The effects of l‐DOPA administration on hypothalamic‐pituitary‐adrenal function were studied in five normal subjects and in five patients with active acromegaly. In acromegalic patients, oral l‐DOPA (500 mg every 4 h for six doses) failed to alter the urinary excretion of 17‐hydroxycorticoids (17‐OHCS), 17‐oxosteroids (17‐OS), and tetrahydro‐11‐desoxycortisol (tetrahydro‐comp S). However, when cortisol synthesis was blocked with oral metyrapone, enhancement of excretion of 17‐OHCS, 17‐OS, and tetrahydro‐comp S by l‐DOPA became apparent in acromegalic patients but not in the normals. In patients with acromegaly, on the day of metyrapone administration, the mean excretion rates of 17‐OHCS, 17‐OS, and of tetrahydro‐comp S were 8.6 mg, 6.4 mg and 4.1 mg/24 h, respectively. When 500 mg l‐DOPA was co‐administered with metyrapone, the corresponding values increased significantly (P<0.01) to 14.9 mg, 9.0 mg and 7.7 mg/24 h. This effect of l‐DOPA was not observed in the normal subjects. It was concluded that l‐DOPA markedly enhanced the hypothalamic‐pituitary‐adrenal response to metyrapone in acromegalic patients, but not in normal subjects. l‐DOPA (or one of its metabolites) probably acts upon a noradrenergic or a dopaminergic system located in the hypothalamus to alter the release of ACTH. The unusual pituitary‐adrenal response to l‐DOPA in acromegaly may reflect: (1) a supersensitive reaction of the pituitary‐adrenal axis to l‐DOPA; (2) a paradoxical response of the pituitary‐adrenal axis to l‐DOPA; or (3) a subtle pituitary‐adrenal dysfunction.

Metabolomics in acromegaly: a systematic review

“…Four studies that did not use MRS or MS-based techniques were excluded from the review. [15][16][17][18] A transcriptomic and a radiomic study were excluded. 19,20 A study performed on animal cell cultures was removed.…”